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	<title>Mannich Rection</title>
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	<h1>1.Summary</h1>
	<img src="1.png"><br /><br />
	<h1>2.Mechanism</h1>
	<h2>Step 1</h2>
	<p>The mechanism of the Mannich reaction starts with the formation of an iminium ion from the amine and the
		formaldehyde. Please note, the mechanism shown below is NOT correct. The pKa of the protonated oxygen is
		approximately -2. The amine base would simply deprotonate the carbonyl and stop the reaction. Consequently, it
		is imperative that this reaction is performed at a pH of approximately 4-5. The correct mechanism should start
		with a nucleophilic attack by the nitrogen atom on the carbonyl carbon.</p>
	<img src="2.png"><br /><br />
	<h2>Step 2</h2>
	<p>The compound with the carbonyl functional group (in this case a ketone) can tautomerize to the enol form, after
		which it can attack the iminium ion.</p>
	<img src="3.png"><br /><br />
	<h2>Step 3</h2>
	<p>On methyl ketones, the enolization and the Mannich addition can occur twice, followed by an β-elimination to
		yield β-amino enone derivatives.</p>
	<img src="4.png"><br />
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	<h1>3.Calculation</h1>
	<img src="mannich.JPG">
	<P>Assuming R=Me</P>
	<h2>Process 1:Formation of Eschenmoser's salt</h2>
	<dl>
		<dd>
			Eschenmoser's salt: N,N-Dimethylmethaniminium<sup>+</sup>
		</dd>
		<dd>
			<img src="process1.JPG">
		</dd>
		<p>
			The first step is that 2° amine attacks the carbonyl to generate <b>1a</b>
		</p>
		<p>
			I use Gaussian16 to optimize the structure of 1a with b3lyp/6-31g(d)
		</p>
		<dd class="title">1a</dd>
		<script>
			jmolApplet(400, "load 1a.pdb", "0");
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		<p>
			not completing......
		</p>
		<p>
			updating......
		</p>
	</dl>
	<h1>4.References</h1>
	<p>
		<a href="https://en.wikipedia.org/wiki/Mannich_reaction">1.Mannich reaction---wikipedia </a>
	</p>
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